November 24, 2020

Early diversity in the firing pattern of embryonic Renshaw cells: just a synergy between two opposite voltage-dependent currents

A remarkable feature of the developing central nervous system is the generation of spontaneous network activity (SNA) at the onset of synaptogenesis. In the spinal cord (SC) of the mouse embryo, SNA occurs around the 12th embryonic day (E12.5) and involves a recurrent functional loop between motoneurons (MNs) and GABAergic interneurons. We previously showed that Renshaw cells (V1R), which constitute a functionally homogeneous population in the adult, are the first neurons enriched with GABA in the mouse embryonic lumbar SC.

V1R make synaptic-like contacts with MNs and likely participate to the genesis of SNA. However, how electrophysiological intrinsic properties of V1R evolve during early development remains poorly understood. Here, using patch-clamp recordings, cluster analysis and biophysical modeling, we analyzed the mechanisms underlying the firing patterns of V1R between E11.5 and E16.5.

This developmental period covers the initial phase of development of SC activity (E11.5-E14.5) when SNA is present, and a pivotal period (E14.5-E16.5) when locomotor-like activity emerges. We discovered that V1R can be subdivided into different clusters before E13.5 and that many cells are capable of sustaining repetitive firing or plateau potentials. These V1R then lose transiently this firing ability, which is later recovered at E16.5. This is in contrast to the classical developmental scheme, i.e. an increase of firing capability with time. Combining pharmacology and computational modeling, we showed that the firing patterns of embryonic V1R rely on the synergy between two opposing voltage-dependent currents, namely the slowly inactivating persistent sodium current and the delayed rectifier potassium current. These two currents are responsible for the repetitive firing of action potentials in a vast majority of neurons. Such a synergy is sufficient to explain the clustering of embryonic V1R and determines the developmental trajectories of the electrical phenotype.

Taken together our findings reveal a simple mechanism that is at the core of the heterogeneity of firing patterns. Such a mechanism must be tuned later on to eventually achieve firing pattern homogeneity.

 bioRxiv Subject Collection: Neuroscience

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